Trends in the Development of New Drugs for Treatment of Benign Prostatic Hyperplasia
Pp. 309-349 (41)
Katarzyna Kulig and Barbara Malawska
Benign prostatic hyperplasia (BPH) is a common condition in aging men that is characterized by nonmalignant enlargement of the prostate gland, and is frequently accompanied by urinary obstruction, and lower urinary tract symptoms (LUST). Currently pharmacotherapy of BPH is based on two classes of drugs: α1-adrenoceptor (α1-AR) antagonists and 5α-reductase inhibitors. It has been shown that α1-AR antagonists reduce symptom scores and increase peak urinary flow rates in BPH. Of particular importance for BPH therapy are uroselective α1-AR antagonists for which the hypotensive related side-effect caused by α1-AR blockade is reduced. 5α-Reductase inhibitors reduce prostate volume and symptom scores, while increasing peak urinary flow rates. This review describes new α1-AR antagonists and 5α-reductase inhibitors in the treatment of BPH and is updating paper published in Current Medicinal Chemistry (Katarzyna Kulig & Barbara Malawska, 2006, 13, 3395-3416). The new α1-AR antagonists represent various structures such as quinazolines, phenylethylamines, piperidines, and arylpiperazines. 5α-Reductase inhibitors are classified into two groups: steroidal and non-steroidal. The newer non-steroidal inhibitors include derivatives of benzo[c]quinolizinones, benzo[f]quinolonones, piperidones and carboxylic acids. Besides the development of new compounds belonging to the above mentioned groups, new agents for BPH treatment are sought among combined 5α-reductase/α1-AR inhibitors, endothelins, androgen receptors antagonists, growth factors, estrogens and phosphodiesterase isoenzymes as well as several phytomedicines, used for prevention and treatment of prostate disorders. These new agents can be used for the design of future targets and development of new drugs in the treatment of BPH. The discovery of a number of active leads may also ultimately help in developing new safe and effective drugs.
Benign prostatic hyperplasia, α1-adrenoceptor antagonists, 5α-reductase inhibitors
Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Medyczna 9 str., 30-688 Kraków, Poland